An insight into the role of barrier related skin proteins |
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Authors: | Wato Kiyomi Hara Takuya Yamana Kenjirou Nakao Hiroshi Inagi Toshio Terada Katsuhide |
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Affiliation: | Fuji Research Laboratories, Pharmaceutical Division, Kowa Company, Ltd., 332-1. Ohnoshinden, Fuji-City, Shizuoka 417-8650, Japan. |
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Abstract: | It is well-known that intercellular lipids in the stratum corneum (SC) of the skin play an important role in maintaining barrier function, and many types of penetration enhancers affecting lipids are used in topical products to improve transdermal drug permeability. Recently, it was reported that functional proteins in tight junctions of the epidermis are important for barrier function. In this study, the effects of penetration enhancers such as fatty esters, amines/amides, and alcohols on the barrier function of the skin were evaluated in rat skin and normal human-derived epidermal keratinocytes (NHEK). All penetration enhancers decreased the electrical impedance (EI), however, the potencies of some penetration enhancers were not equal between rat skin and NHEK. The differences were clarified by immunohistochemical studies: some fatty esters decreased the immunoreactivity of involucrin and keratin 10 in the upper layer of the epidermis, while alcohols decreased the immunoreactivity of desmoglein-1, claudin-1, and E-cadherin located in the lower layer of the epidermis. From these results, it is suggested that penetration enhancers show new action mechanisms disturbing barrier-related proteins in epidermis, which are classified into two categories depending on their action sites. |
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Keywords: | NHEK, normal human-derived epidermal keratinocytes SC, stratum corneum EI, electrical impedance ER, enhancement ratio IP, irritation potential DID, diisopropyl adipate DS, diethyl sebacate IS, diisopropyl sebacate IM, isopropyl myristate NMP, n-methylpyrrolidone CT, crotamiton UR, urea OA, oleyl alcohol LA, lauryl alcohol PG, propylene glycol S80, sorbitan monooleate LM, lauromacrogol T20, polysorbate 20 SLS, sodium lauryl sulfate TEWL, transepidermal water loss |
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